ABSTRACT

The limbs of higher vertebrates develop from lateral buds consisting of a somatic mesodermal core, surrounded by an ectodermal epithelium. The anlage of the forelimb is located adjacent to somites 16-21 (Zhi et al., 1996), while the hindlimb forms at the level of somites 26-32 (Jacob et al., 1979). The shape of differentiated fore-and hindlimbs (arm-leg; wingleg) may differ considerably, however, it is becoming more and more obvious that the fundamental gene regulatory and morphogenetic mechanisms of limb development are highly conserved (for review see: Morgan and Tabin, 1993; Tabin, 1995; Tickle, 1995; Niswander, 1997). Most of our knowledge on limb development is derived from molecular studies on murine and avian embryos, and many experimental studies employing micro-surgical techniques have been performed on avian and amphibian embryos. These studies have shown that the positioning of the limb anlagen is determined by genes that, in sum, establish the so-called hox code (Charité et al., 1994; Cohn et al., 1997). The specific expression pattern of Hox9 genes in the somatic mesoderm of wing, flank and leg level is crucial for the positioning of limb buds and their specification into wing or leg (Cohn et al., 1997). Outgrowth and patterning of the limbs is controlled by a cascade of regulatory genes involving Fibroblast Growth Factors (FGFs), Bone morphogenetic proteins (Bmps), Sonic hedgehog (Shh), Radical fringe and Wnts (Peters et al., 1992; Riddle et al., 1993; Dealy et al., 1993; Echelard et al., 1993; Niswander et al., 1994; Cohn et al., 1995; Crossley and Martin 1995; Laufer et al., 1997).